C Edmead Lec 5

Question 1

MMPs are a family of enzymes involved in joint destruction in RA

Degrade bone and cartilage and promote ______ (formation of new blood vessels).

MMPs _____ circulating TNF levels by cleaving TNF from cells.

Trocade - is specific for collagenases and was trialled in RA patients but stopped due to ___ efficacy.

Move towards more specific MMP inhibition (eg Gelatinase A) As if we can inhibit the production of MMPs then we can ____ the levels of circulating TNF.

Answer 1

Angiogenesis

Increase

Low

Decrease

Question 2

Immunosuppresants:

Eg Cyclosporin and Tacrolimus

They are ____ peptides

Mainly used in ____ _______ to prevent rejection

Selective effects on _ lymphocytes

Prevents clonal expansion (signalling) (IL-2 and IL-2R)

Bind immunophilins and inhibit gene ________.

BUT there is a risk of ______.

Answer 2

Fungal

Organ transplantation

T

Transcription

Infection

Question 3

Type IV PDEIs eg rolipram – increase c___ and suppress ___ translation

Cytotoxic agents – azathioprine and cyclophosphamide

Omega 3 – ___ doses change AA metabolites to ___ and LTB5 – less inflammatory

Answer 3

cAMP

TNF

HIGH

PGE3

Question 4

Anti IL- 6 agents such as Tocilizumab have been used.

IL - 6 drives/contributes to ____ in joints (sinusitis).

Useful for patients that cant tolerate anti-___.

Answer 4

Inflammation

Anti-TNFs

Question 5

Can use oral ICE inhibitors.

ICE cleaves __-_ from it’s propeptide form.

Answer 5

IL-1

Question 6

Can use 5 lipoxygenase inhibitors too.

These will prevent the production of ______.

e.g Zileuton

Answer 6

Leukotrienes

Question 7

IL-17 is produced by activated Type 17 _ ___ cells (TH17)

Present in _____ joints

Synergises with and enhances effects of ___

Can upregulate NFkB, MAPK, IL-6, COX-2 and NO

α-IL-17 effective __ _____ agent

Answer 7

T helper

Inflamed

TNF

ANTI INFLAMMATORY

Question 8

Regulatory T cells:

Suppressor T cells
CD4+, CD25+, Fox-3 + T cells

Natural and adaptive T regs

______ down immune cell activation

Secrete anti inflammatory _____ eg IL-__, TGF-β

Answer 8

Dampen

Cytokines

IL-10

Question 9

Areas of interest:

Look at ways of reducing presentation of ____ ____to T cells or prevent activation of T cells (costimulation).

Modulatory APCs (e.g dentdritic cell) reduce ability of _____ and B cells to present ____ to T cells – stop presenting ___ ____, stop cycling of pathway

Increase Th/c anergy (angergic = unresponsive)/apoptosis so reduce number of self reactive cells in periphery

Increased levels of regulatory T cells to ____ _____ the immune system.
CD28 B7 = main one (co stimulatory)

Answer 9

Self antigen

Macrophages

Antigen

Self antigen

Dampen down

Question 10

In B cells:

B cells in RA patients show increased B7-2 (other half of CD28 link – so increased stimulation) and decreased Fc Recptor (less dampening down signal for B cells)

B cells can present antigen to T cells and activate them.
Anti TNF (tumour necrosis factor) therapy \_\_\_\_\_ expression of B7-2 – less ability to stimulate _ cells so help so dampen down \_\_\_\_\_\_.

So anti TNF doing more than just mopping up TNF – more global response

Answer 10

Decreased

T cells

Inflammation